Renal denervation restores the baroreflex control of renal sympathetic nerve activity and heart rate in Wistar-Kyoto rats with cisplatin-induced renal failure S. A. Khan, 1 M. A. Sattar, 1 H. A. Rathore, 1 M. H. Abdulla, 3 F. ud din Ahmad, 1 A. Ahmad, 1 S. Afzal, 1 N. A. Abdullah 2 and E. J. Johns 3 1 Department of Physiology, School of Pharmaceutical Sciences, Universiti Sains Malaysia, Penang, Malaysia 2 Department of Pharmacology, Faculty of Medicine, Universiti Malaya, Kuala Lumpur, Malaysia 3 Department of Physiology, University College Cork, Cork, Ireland Received 23 August 2013, revision requested 4 October 2013, revision received 4 December 2013, accepted 10 January 2014 Correspondence: E. J. Johns, Department of Physiology, Uni- versity College Cork, Western Gateway Building, Western Road Cork, Ireland. E-mail: e.j.johns@ucc.ie Abstract Aim: There is evidence that in chronic renal failure, the sympathetic ner- vous system is activated. This study investigated the role of the renal innervation in suppressing high- and low-pressure baroreflex control of renal sympathetic nerve activity and heart rate in cisplatin-induced renal failure. Methods: Renal failure was induced using cisplatin (5 mg kg À1 , i.p.) and the rats used 7 days later. Groups of rats were anaesthetized and prepared for measurement of renal sympathetic nerve activity and heart rate. Acute unilateral or bilateral renal denervation was performed, and renal sympa- thetic nerve activity and heart rate baroreflex gain curves were generated while the cardiopulmonary receptors were stimulated using an acute saline volume load. Results: Cisplatin administration reduced (P < 0.05) glomerular filtration rate by 27%, increased sodium fractional excretions fourfold, plasma creatinine and kidney index by 39 and 30% respectively, (all P < 0.05) compared with control rats. In the renal failure rats, baroreflex sensitivity for renal sympathetic nerve activity and heart rate was reduced (P < 0.05) by 29% and 27% (both P < 0.05) compared with control animals. Bilat- eral, but not unilateral, renal denervation restored baroreflex sensitivity to normal values. Volume expansion reduced (P < 0.05) renal sympathetic nerve activity by 34% in control rats, but remained unchanged in the renal failure rats. Unilateral and bilateral renal denervation progressively restored the volume expansion induced renal sympathoinhibition to control values. Conclusion: These findings reveal a significant role of the renal sensory innervation in cisplatin-damaged kidneys which blunt the normal barore- flex control of renal sympathetic nerve activity. Keywords baroreceptor reflexes, cisplatin-induced renal failure, renal denervation, renal sympathetic nerve activity. The kidney receives a rich supply of both afferent sensory and efferent sympathetic innervations (Johns et al. 2011). The efferent sympathetic fibres originate from spinal segments T11- L3 and give rise to the post-ganglionic fibres which innervate all essential parts of the kidney including arterioles, renal tubules and vessels. There is also an afferent or sensory inner- vation arising mainly from the pelvic area but also to © 2014 Scandinavian Physiological Society. Published by John Wiley & Sons Ltd, doi: 10.1111/apha.12237 690 Acta Physiol 2014, 210, 690–700